Contribution of a voltage-sensitive calcium release mechanism to contraction in cardiac ventricular myocytes.
The contribution of a voltage-sensitive release mechanism (VSRM) for sarcoplasmic reticulum (SR) Ca2+ to contraction was investigated in voltage-clamped ventricular myocytes at 37 degrees C. Na+ current was blocked with lidocaine. The VSRM exhibited steady-state inactivation (half-inactivation voltage: -47.6 mV; slope factor: 4.37 mV). When the VSRM was inactivated, contraction-voltage relationships were proportional to L-type Ca2+ current (ICa-L). When the VSRM was available, the relationship was sigmoidal, with contractions independent of voltage positive to -20 mV. VSRM and ICa-L contractions could be separated by activation-inactivation properties. VSRM contractions were extremely sensitive to ryanodine, thapsigargin, and conditioning protocols to reduce SR Ca2+ load. ICa-L contractions were less sensitive. When both VSRM and ICa-L were available, sigmoidal contraction-voltage relationships became bell-shaped with protocols to reduce SR Ca2+ load. Myocytes demonstrated restitution of contraction that was slower than restitution of ICa-L. Restitution was a property of the VSRM. Thus activation and recovery of the VSRM are important in coupling cardiac contraction to membrane potential, SR Ca2+ load, and activation interval.
Howlett
S E
SE
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Zhu
J Q
JQ
Ferrier
G R
GR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D006168:Guinea Pigs; D006352:Heart Ventricles; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D026941:Sodium Channel Blockers; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D026941:Sodium Channel Blockers; D012433:Ryanodine; D019284:Thapsigargin; D008012:Lidocaine; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium